To study the effect of hesperidin on peroxisome proliferator-activated receptor alpha(PPARα)and sterol regulatory element binding protein 1 c in high-fructose and high-fat diet-induced non-alcoholic fatty liver disease(NAFLD)mice.Methods:A total of 60 male Kunming mice were randomly divided into a normal group，a model group，a positive drug polyene phosphatidylcholine group，and a hesperidin low，medium and a high dose groups，with 10 in each group.Except for the normal group being fed with ordinary feed and ordinary water，the other 5 groups were fed with 10% fructose water+high-fat feed for 8 weeks to construct a NAFLD model.After 4 weeks of treatment，the mice were sacrificed and detected the liver function AST，AST，blood lipids and hepatic lipids TG，TC.Liver pathology was observed and the expression of PPARα and SREBP-1c protein and mRNA in liver tissue was detected.Results:Hepatic pathology HE staining showed that the slices in normal group was normal，and in the model group showed obvious fat vacuoles.Compared with the model group，each observation group were improved significantly.Compared with the normal group，AST，ALT，serum TG，serum TC，liver TC and liver TG in the model group were significantly increased(P<0.05)，and the observation groups were significantly lower than them in the model group(P<0.05)，there was no difference between the hesperidin high dose group and the polyene phosphatidylcholine group.Compared with the normal group，the PPARα was significantly lower in the model group(P<0.05)，SREBP-1c was significantly higher(P<0.05)，and the PPARα was significantly increased after hesperidin treatment(P<0.05)，and SREBP-1c was significantly lower(P<0.05).In addition，there was no difference between the high dose hesperidin group and the polyene phosphatidylcholine group.Conclusion:Hesperidin can significantly reduce the expression of SREBP-1c in the liver tissue of NAFLD mice induced by lowing high fructose+high fat diet，and increase the expression of PPARα，thereby regulating blood lipids and protecting liver.